Lymphocyte Involvement in Rheumatoid Arthritis

Paulus, Harold E.; Machleder, Herbert I.; Levine, Seymour; Yu, David Tak Yan; MacDonald, Norman S.

doi:10.1002/art.1780200614

Cited by 185 publications

(46 citation statements)

References 39 publications

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“…Therapies targeting T lymphocyte populations have produced some clinical improvement, but few studies have examined the effect on articular destruction (9- 13,29,30). Where this has been examined, progression of articular destruction has been demonstrated (3 1).…”

Section: Discussionmentioning

confidence: 99%

Synovial tissue macrophage populations and articular damage in rheumatoid arthritis

Mulherin

FitzGerald

Bresnihan

1996

Arthritis & Rheumatism

453

310

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Objective. To examine the relative contribution of individual synovial cell populations to polyarticular destruction in rheumatoid arthritis (RA).Methods. Serial measurements of disease activity and articular destruction, obtained prospectively in 28 RA patients followed up for a mean of 5.8 years, were correlated with synovial cell populations quantified using immunohistochemical techniques.ResuZts. The mean radiologic score worsened (from 37 to 86; P = 0.OOOl) despite significant improvement in disease activity. Synovial lining layer cell depth and sublining layer macrophage, but not lymphocyte, cell counts correlated significantly with radiologic course. Detailed analysis of 11 patients demonstrated reduced synovial lining expression of CD14 compared with CD68 (P = 0.003), whereas sublining expression of CD14 and CD68 was equivalent. Conclusion. Synovial macrophage numbers correlated with articular destruction in RA. In addition, the study results provided further evidence that lining layer macrophages may represent a distinct subpopulation that is of importance in this process. These findings have implications for the development of new therapies for RA.Rheumatoid arthritis (RA) is characterized by synovial membrane inflammation leading to chronic polyarticular destruction (1,2). Increased lining layer cell depth is prominent, primarily as a result of accumulation of type A macrophage-derived lining cells, with some local proliferation of type B fibroblastDr. Mulherin

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Section: Discussionmentioning

confidence: 99%

Synovial tissue macrophage populations and articular damage in rheumatoid arthritis

Mulherin

FitzGerald

Bresnihan

1996

Arthritis & Rheumatism

453

310

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“…Many observations suggest that T lymphocytes contribute significantly to the disease process in RA [1][2][3][4]. Several anti-CD4 MoAbs have been shown to be successful in treating RA [5][6][7][8][9][10][11], although some randomized studies have given negative results [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Treatment with an anti-CD4 monoclonal antibody strongly ameliorates established rat adjuvant arthritis

Pelegrí

Morante

Castellote

et al. 1996

Clinical and Experimental Immunology

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SUMMARYSome experimental arthritic diseases can be prevented by treatment with anti-CD4 MoAbs. Trials with ongoing disease have not been successful so far. The aim of this study was to ascertain whether W3/25 could reverse adjuvant arthritis (AA), when beginning treatment on day 14, i.e. when the disease was established. Moreover, one group of animals treated with the anti-CD4 MoAb received OX8 MoAb at the same time, thus depleting CD8 cells from circulation. During treatment with W3/25, a strong amelioration of inflammatory signals was observed, as assessed by means of paw volume increase and arthritic score. However, when treatment stopped, a rebound to arthritis signals occurred. The parallel depletion of CD8 cells did not modify these effects, thus the combined treatment W3/25 OX8 gave the same amelioration as treatment with W3/25 alone. These findings indicate that CD4 cells play an important role in perpetuating rat AA. Moreover, CD8 cells do not seem to have a regulatory role in the CD4 cells responsible for the inflammatory response.

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“…A double-blind clinical trial is warranted to determine its clinical efficacy in treating RA. Dw 14,and Dwl5) are associated with susceptibility t o RA (4-7); 4) improvement in preexisting RA in some patients developing acquired immunodeficiency syndrome (AIDS) (8); and 5 ) improvement in refractory RA following thoracic duct drainage (9).…”

mentioning

confidence: 99%

Use of a chimeric monoclonal anti‐CD4 antibody in patients with refractory rheumatoid arthritis

Moreland

Bucy

Tilden

et al. 1993

Arthritis & Rheumatism

127

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Objectives. To evaluate the safety, immunogenicity, and biologic effects of chimeric monoclonal anti‐CD4 (cM‐T412) in patients with refractory rheumatoid arthritis (RA), and to obtain preliminary data on the clinical response to this treatment.Methods. Twenty‐five patients with active refractory RA were treated with incremental doses (10 to 700 mg) of cM‐T412 in an open‐label, escalating‐dose phase I trial.Results. Infusion with cM‐T412 was followed by an immediate, rapid decline in CD4+ T cells. The level of circulating CD4+ T cells remained depressed in most patients even at 6 months posttreatment. Following antibody infusion, proliferative responses of peripheral blood lymphocytes to mitogens and antigens were determined; mitogen and antigen responses were decreased compared with pretreatment responses. Mitogen responses tended to return to baseline values more rapidly than did responses to antigen. Adverse events included fever (19 patients), which was associated with myalgias, malaise, and asymptomatic hypotension; these symptoms were self‐limited and appeared to correlate with transient elevations in interleukin‐6. No significant human antibody response to the cM‐T412 variable region was detected; only 2 patients developed transiently low levels of antibodies reactive with cM‐T412. Significant clinical improvement, defined as ≥50% decrease in tender joint counts compared with baseline, was noted in 43% of patients at 5 weeks and 33% at 6 months following cM‐T412 infusion.Conclusions. Treatment of refractory RA with cM‐T412 appears to be safe and is associated with sustained decreases in circulating CD4+ T cell counts and depressed in vitro T cell responses. No significant human antichimeric antibody response was detected. Nonblinded assessment of clinical end points suggests that treatment with cM‐T412 may have beneficial effects in these patients with refractory RA. A double‐blind clinical trial is warranted to determine its clinical efficacy in treating RA.

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Lymphocyte Involvement in Rheumatoid Arthritis

Cited by 185 publications

References 39 publications

Synovial tissue macrophage populations and articular damage in rheumatoid arthritis

Synovial tissue macrophage populations and articular damage in rheumatoid arthritis

Treatment with an anti-CD4 monoclonal antibody strongly ameliorates established rat adjuvant arthritis

Use of a chimeric monoclonal anti‐CD4 antibody in patients with refractory rheumatoid arthritis

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